Characteristics of benzo[a]pyrene and A-ring reduced 7,12-dimethyl benz[a]anthracene induced neoplastic transformation of human cells in vitro.
The polynuclear aromatic hydrocarbons (PAH) benzo[a]pyrene (BP) and the A-ring reduced analogue of 7,12-dimethylbenz[a]anthracene (DMBA), 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene (TH-DMBA) are carcinogenic to human cells. The unsaturated PAH, DMBA exhibits no carcinogenic activity on human cells as measured by growth in soft agar. The TH-DMBA and BP treated cells exhibit a colony frequency in soft agar of 84 and 86, respectively. These anchorage independent cells, when seeded on the chick embryonic skin (CES) organ cultures, are invasive and form a fibrosarcoma. It is highly unlikely that TH-DMBA, which does not contain an aromatic A-ring, can undergo metabolism in human cells in culture to form a bay region 3,4-dihydrodiol-1,2-epoxide. These results suggest that an alternate mechanism for the induction of carcinogenesis is appropriate to explain the absence of bay region diol-epoxide metabolite as the ultimate form of the carcinogen in TH-DMBA induced carcinogenesis in human diploid cells.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D006801:Humans
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D015127:9,10-Dimethyl-1,2-benzanthracene; C033113:1,2,3,4-tetrahydro-7,12-dimethylbenz(a)anthracene